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Voice-over: Welcome to Spotlight on Migraine hosted by the Association of Migraine Disorders. Join us for fresh perspectives by medical experts and advocates as we explore the spectrum of migraine and dig deeper into this complex disease. Thank you to our 2023 education sponsors.

Nerivio is a neuromodulation device that has been approved for the acute and preventive treatment of migraine for people aged 12 years and older. But how does it work? Who can use it? Tune in as we answer these questions and more with Theranica’s CEO and Co-founder, Alon Ironi.

Molly O’Brien: Hello and welcome to Spotlight on Migraine. I’m your host Molly O’Brien. Today we’re talking about a deep dive into a migraine treatment device, no drugs involved. It’s called the Nerivio. And I’m very pleased to welcome our guest, Alon Ironi. He is Theranica’s CEO and Co-founder. Theranica is the digital therapeutics company that created Nerivio, a neuromodulation device for migraine. Alon, thank you so much for joining us today.

Alon Ironi: Thank you for having me, good morning.

O’Brien: Hello. We’re so excited to talk about this device. Now Nerivio has been around for a while, but we have some updates and exciting news to share with our followers.

So let’s start off with the very basics, what is Nerivio?

Ironi: So, Nerivio is a drug-free, wearable, remote, electrical neuromodulation device. It’s digitally operated by smartphone application. Every migraine treatment lasts 45 minutes, but it takes only one minute to start the treatment, and then you can go about your daily routine.

O’Brien: So some people might be familiar with neuromodulation, but others may not. Some people might just be getting into this. Can you tell us about how Nerivio works to help fight migraine?

Ironi: Yes, absolutely. There are several kinds of different types of neuromodulation, specifically remote, electrical neuromodulation, which is the technology deployed by Nerivio, works like this. Nerivio is placed on the upper arm, and then it applies to the skin an electrical current, waveform, especially designed to activate nociceptive nerve fibers or fiber receptors under the skin.

These nerve fibers serve as ascending pipes for transferring pain signals up to the brain. The signals are then processed in the brain processing center, the brain stem, processing center. They trigger a pretty powerful descending pain inhibition pathway which is called conditioned pain modulation, CPM.

And this results with increased release of two analgesic neurotransmitters, serotonin and norepinephrine, directly into the migraine pathway in the brain, which inhibits the signaling of migraine pain and other migraine symptoms.

O’Brien: That’s absolutely fascinating and again, you have been around, Nerivio has been around for a couple of years, but we have some exciting news. Before Nerivio was only cleared for acute treatment or abortive treatment, and now Nerivio has clearance for prevention.

So can you tell us a little bit about how people can use Nerivio, let’s start there?

Ironi: Right. So like you said, the initial indication about three years ago, indication for use, was for acute treatment, meaning upon onset of the migraine attack. And then, following a recent placebo-controlled study in prevention of migraine, which demonstrated strong efficacy in reducing migraine days, headache days, and days of medication, the indication was expanded last month to preventive treatment as well.

So the present indication, the new indication for use, is actually for acute and/or prevention of migraine, with or without aura in patients at the age of 12 or above, which includes both chronic and episodic migraine patients.

O’Brien: Good news for kids out there that live with migraine; you know, 12 and older, that’s super exciting. Can you tell us a little bit more about how we can use the device? So meaning if you’re currently using it for acute treatment, can you also use it for prevention? And if you want to use it for prevention, can you also use it for acute treatment? Can you do both, how do you use it?

Ironi: Yes, this can be confusing, but it’s actually very simple. So for preventive use, patients who’ve used the Nerivio every other day – so that means 15 times per month – they can choose any time of the day to do so. The Nerivio application actually can send patients a notification reminding them to apply a preventive treatment on days that they chose, every other days that they chose, and at whatever hour they set. So that’s for preventive.

Now for acute patients who just use the device whenever needed, meaning, whenever they feel the onset of a migraine attack, this could be the appearance of pain, or aura, etc. And, of course, for acute – and this is true for every acute therapy – early treatment is recommended rather than waiting for the full, you know, manifestation of the migraine attack.

Now, when you talk about dual use, both prevention and acute, there are several questions that I’m happy to clarify. So the concept of dual use is really, at least in the case of the review, use every other day for prevention plus whenever needed.

And let me give you some examples. Let’s say you were planning to use Nerivio on let’s say Thursday afternoon for prevention, as part of your every other day modality. But, unfortunately, you got a migraine attack on Thursday morning. So, you use the Nerivio for acute, and that treatment would also count as your preventive treatment for the day.

So your next treatment for prevention will be on Saturday, unless you need another acute treatment. Or let’s take another example. You used Nerivio already on let’s say Thursday morning for prevention, and then you happen to have a migraine attack on Thursday afternoon. This is not very common, but it could happen. Then you use it again, even though you used it in the morning, a few hours ago, you just use it again, this time for acute. And then again your next scheduled treatment is going to be Saturday, two days from now.

So this is important because of the safety profile of Nerivio, there’s no limitation on how many times let’s say how many doses per week, day, month, and so on. So you’re not, there’s no limitation, just use it every other day as a basis and then whenever needed.

O’Brien: That is a very…it’s hard to follow along with, but it’s not, because when you say it at the end, you wrap it up, it’s like, you use it every other day, unless you need it more. And then you use it when you need it.

Ironi: Exactly.

O’Brien: And you talked just briefly there because the safety profile of the device, it’s safe, it’s very safe for use. So, talk to us a little bit about possible side effects that people might have with use, or something that people might see if there is any safety indications the user should know about.

Ironi: Well, first of all, yes, the safety profile is very high. The rate of device-related adverse events or side effects is very low. They’re all local; in other words, none of the side effects is systemic. Local meaning that this could be tingling in the arm or numbness in the arm or redness in the arm right under the electrodes. So they’re all local, they’re all mild, and they’re all temporary so they don’t need any intervention. Typically they disappear, if they appear at all, they disappear within 10 to 15 minutes after the end of the treatment.

So that’s one. Now there are, of course, certain contraindications. So there are actually two. Nerivio should not be used by people who have an implanted electrical device that cannot be turned off during the treatment, for example a pacemaker, right? So, this is where Nerivio should not be used. It should also not be used by people who have active epilepsy attacks. These are the only two contraindications.

When you use it on the arm, make sure you put it, you place the device over healthy skin.

O’Brien: Okay, that’s good to know as well. So let’s talk a little bit about some of the benefits of using Nerivio. Obviously, the biggest one, in my opinion, is it’s nonpharmaceutical. There are no drugs involved. So that can really, really be a great option for people who can’t tolerate taking a medication, who can’t physically swallow, who are possibly taking too much medication and then switch over into rebound or medication overuse headache. So that’s just, for me, one of the biggest ones that stands out. What are some of the other benefits of using a Nerivio device, either for prevention or for acute treatment?

Ironi: Yeah, for both. Well we touched, I think, at least one of them, which is the safety. You know, the fact that very low rates of side effects, all of them local and temporary, and so on. That’s very important, together with the fact that there’s no limitation on the number of usages and so on.

So that’s number one. Safety first, right? The efficacy, as was demonstrated in multiple studies, is very high. I mean, we can dive in later to the numbers, if you want, but it does have a very high efficacy profile along several different clinical studies in different populations, different people with migraine.

And then, now with the dual use indication, it makes it very easy for patients to use. They don’t need to carry around with two different therapies. They can focus on one. And that helps adherence, and good adherence always helps efficacy, both on prevention and acute So, that’s an advantage by itself.

Other advantages are that it is discreet. So the device is slim, and it fits under a sleeve. So, for example, adolescents can use it in the classroom. Their classmates don’t even have to know that they’re going through a therapy right now. And I think that’s an advantage for some people.

And then last but not least, on top of the treatment itself, the Nerivio application provides a comprehensive migraine diary, which is shareable with your healthcare provider. It provides personalized tips on how to improve your adherence and outcomes based on your own history. And it has a built-in CBT tool for reducing stress during and in between the migraine attacks. It’s part of the application.

O’Brien: You did talk, just briefly, about the efficacy as being a benefit. Let’s talk about that. Because some people might hear, if they’re not super familiar with neuromodulation as a treatment option, they might say, what, I don’t have to take a pill? There’s no way it works. But it does, in fact. So talk to us a little bit about the efficacy.

Ironi: So, if you look at the various clinical studies done with Nerivio over the last few years, then starting with acute treatment, let’s take two examples. The rate of post-two-hour pain relief, post-two hour is the Holy Grail for measurements, for acute treatment. So, for post-two-hour pain relief, which is going from moderate to severe level of pain down to either mild or no pain, the range that we record in our studies were anywhere between 62% and 72% of the users, depending on the population.

We had a little higher efficacy among adolescents, a little lower in chronic compared to episodic, but that’s common to all drugs. So 62 to 72% for pain relief.

For pain freedom, which is complete disappearance of the pain, post-two hours, the results were anywhere between 25, 26% for chronic up to 37, 38% for adolescents and in episodic patients. And that’s with respect to acute. Of course, there are other endpoints but, I mean, we have this information on our website.

Now for preventive, the average reduction of migraine days per month was four. So four migraine days less than the baseline, and four-and-a-half headache days less than the baseline. So a reduction of four migraine days and four-and-a-half, 4.5, headache days on average.

Then we have more than 50%, I think 51% of the patients reporting at least 50% reduction in their monthly days of moderate or severe headache. And this is moderate or severe headache days, as you know, this is the biggest enemy. This is where you get debilitated and so on. So more than half of the patients reported reduction of more than 50% in that parameter.

So together, if you look at the acute and preventive results together, I can objectively say that this places the review among the top treatments for migraine relief.

O’Brien: That’s so cool. It’s alarming when you say back the numbers. I mean, taking four headache days away and reducing severe and moderate headache that’s phenomenal. It’s very exciting and good news for people out there living with migraine.

Let’s talk a little bit about who’s a good candidate to use the device either for prevention or for acute.

Ironi: Good question. First of all, the truth is Nerivio may benefit almost every person with migraine. But that said, looking at the data we’ve accumulated, it is especially recommended for, I guess, five or six specific types of patients.

First is adolescents because most of the medications indicated for migraine are not approved, not indicated yet, for adolescents, so they have less, or let’s say a smaller range of alternatives or possibilities. So Nerivio is highly recommended for adolescents, even more than the general population.

Then, patients, and you said it before, patients who failed on drugs, either because of lack of efficacy or because of intolerability to the side effects, obviously, should definitely try Nerivio.

People whose occupation requires them to stay sharp and focused because some of these medications, not all of them, but some of them might cause fatigue or some sort of disorientation. And so people, you know, truck drivers, bus drivers, teachers, police officers, healthcare providers, athletes, these kind of people definitely could benefit from a drug-free remedy or a drug-free therapy.

And another thing you mentioned is people who just can’t use migraine drugs, either because of their comorbidities, some other limitations, or simply a risk of interaction with other drugs. Drug-drug interaction with other drugs that they’re taking.

One specific group is people who are at risk of medication overuse headache already suffering from MOH. So, if you look at the recommendations of the American Headache Society, then the maximum monthly dosage of prescribed therapies for migraine is 10 or 9, depending on which type. And so what would you do if you have 11 or 15 or 17 migraine attacks per month? Again, Nerivio could be a great option for these people.

And finally, we have a lot of patients that just prefer a healthy lifestyle, minimizing the usage of chemical agents, and so on, and so they’re happy to use something that is drug free.

O’Brien: I want to just double-check and make sure because we’re talking about who’s a good candidate. People who should not use a Nerivio device are those who have an implant that cannot be turned off such as a pacemaker during use. And those with epilepsy, is that correct?

Ironi: Either that or active epilepsy attacks. So again, it’s really difficult to think of someone who wouldn’t benefit from Nerivio. But I would say honestly, that if you have migraine, and you’re just satisfied with the medication you take, you get good efficacy, no side effects, keep it going. Like they say, if it ain’t broke, don’t fix it, right?

O’Brien: Exactly. Let’s talk about how to get the best use from a treatment. You mentioned treat it as early as possible. So what does that look like, and are there any other tips to get the best effects of the Nerivio device?

Ironi: Really very simple set of rules. For prevention, just keep using it every other day. I mean, if you miss one or two days a month, nothing happens, but try not to miss and just keep doing it every other day. That’s for prevention. That’s pretty easy.

For acute, the most important thing – and again, this is common to all acute medications or therapies for migraine – is don’t wait, don’t let the migraine attack develop into a fully blown manifestation. Especially with drug-free therapy, if you’re in doubt, there’s no doubt. If you think that you have a migraine, go ahead and use it. You have aura, you have pain, you think that it is a migraine, there’s nothing to lose, just use it.

We did find, in our studies, that patients who use the device within one hour from the onset have higher response rate by about 10% compared to patients that just waited more than one hour. But again, this is common for most of the acute medications.

O’Brien: Okay, so the sooner the better. Let’s talk about, again, back to some basic details. How do I get a device? How does someone out there, if they’re interested, they see this podcast, how can they go ahead and access the device?

Ironi: Well, obviously, it’s a prescribed therapy, so you need to get a prescription from your physician. On our website, there’s a way to download a prescription form because some physicians, especially primary care physicians, are still not familiar with Nerivio. So you can download the prescription form, bring it over to the clinic or send it over to them. They can click and get some information from our website if they’re really not familiar with the device, and then they prescribe. Of course, if you go to a clinic that has already been working with Nerivio, that’s even easier.

Once you get the prescription, then it is sent either as an electronic script or by fax to one of our specialty pharmacy partners, and then they contact the patient and do the dispense.

We also have a telemedicine service that is operated by a partner. There’s access from our website and patients can simply go there, they click, they schedule a virtual appointment. They get the prescription after filling out a questionnaire based on if they’re adequate for that. That’s it. It’s sent to their home. These are the two ways to get the device.

O’Brien: Wonderful. And then, how many treatments do you get with the device? Is it going to be the same now for prevention and acute treatment, or how many treatments do you get?

Ironi: When we first launched the device, it was 12 treatments. But now starting from April actually, it is changed to 18. So 18 treatments per one device, one unit. Which, if you think about using the device every other day for prevention, plus for some acute treatments, it pretty much means one device per month for dual use.

O’Brien: And as we’re wrapping up here, is there anything else you think people should know about the Nerivio device for migraine treatment?

Ironi: I think we covered it pretty well. And I invite people to follow our website. We keep coming up with new clinical data. We put strong emphasis on creating more and more clinical data, working with patients in clinics and so, it’s important for us to provide this information to providers as well as patients.

O’Brien: Exactly. Well thank you so much for joining us today and thank you all for watching. I’d really like, again, to thank our guest, Alon Ironi, who is the CEO and co-founder of Theranica, the makers of Nerivio.

Again, thanks so much for joining us, Alon.

Ironi: Thank you, Molly, for giving me the opportunity.

O’Brien: Love hearing about the Nerivio device. And thank you to all of you out there who are listening, watching, and following along. With the Association of Migraine Disorders, I’m Molly O’Brien. We’ll see you next time.

Voice-over: Thank you for tuning into Spotlight on Migraine. For more information on migraine disease, please visit MigraineDisorders.org.

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*The contents of this podcast are intended for general informational purposes only and do not constitute professional medical advice, diagnosis, or treatment. Always seek the advice of a physician or other qualified health provider with any questions you may have regarding a medical condition. The speaker does not recommend or endorse any specific course of treatment, products, procedures, opinions, or other information that may be mentioned. Reliance on any information provided by this content is solely at your own risk.